Identification of Natural Products for the Treatment of Alzheimer’s Disease: 3D Similarity Search
Glycogen synthase kinase-3 (GSK-3), one of the main tau kinases involved in a variety of cellular processes, has been evidenced as a promising target for Alzheimer’s disease (AD) treatment. In recent years, great efforts have been made to discover new molecules with an enhanced profile that inhibit GSK-3 and display efficacy in AD treatment. SAR502250, a newly discovered selective GSK-3 inhibitor with AD therapeutic potential, represents a good alternative to design future specific inhibitors against this condition. SAR502250 was used as a query in a 3D similarity search on the SPECS database to select new natural compounds as possible GSK-3 inhibitors. According to ShapeTanimoto, TanimotoCombo, and ComboScore matrics, the first 10 SPECS natural compounds were selected and structurally analyzed. The ADME (Absorption, Distribution, Metabolism, and Excretion), physicochemical parameters, and toxicity-related risk profiles of the selected natural compounds were also investigated. The 3D similarity results in conjunction with pharmaceutical profiles revealed the potential use of natural compounds as GSK-3 inhibitors for Alzheimer’s disease therapy.